CASE OF THE WEEK
PROFESSOR YASSER METWALLY
A 64 years old female patients presented clinically with sudden onset of right hemiplegia and global aphasia.
Figure 1. Late subacute hematoma. A CT scan image showing the hematoma as an oval hyperdense space occupying
lesion with positive mass effect. The lesion is surrounded by a hypodense edema rim. The increased protein content of
the retracted clot is responsible for the high attenuation noted on noncontrast CT. B,C precontrast MRI T1 images. The
subacute hematoma has a hyperintense peripheral rim (due to extracellular methemoglobin) and a central isointensity
mostly due to Paramagnetic intracellular deoxyhemoglobin.
Figure 2. Late subacute hematoma. MRI T2 images. The subacute hematoma has a hyperintense peripheral rim (due to
extracellular methemoglobin) and a central hypointensity mostly due to Paramagnetic intracellular deoxyhemoglobin.
Edema could also contribute to the peripheral T2 hyperintensity.
Figure 3. Late subacute hematoma. MRI
FLAIR images. The subacute hematoma
has a hyperintense peripheral rim (due to
extracellular methemoglobin) and a
central iso to hypointensity mostly due to
deoxyhemoglobin. In this patient the
appearance of the subacute hematoma on
FLAIR images is similar to that seen on
MRI T2 images. Edema could also
contribute to the peripheral T2
Figure 4. Diffusion weighted images. The appearance of hemorrhage on DW MR images is complex and involves many
factors, including the relative amounts of different hemorrhagic products and the pulse sequence used. Oxyhemoglobin
is hyperintense on DW images and has a lower ADC than does normal brain tissue; this may indicate the relative
restriction of water movement inside the red blood cell (101). Extracellular methemoglobin has a higher ADC than does
normal brain tissue, which indicates that the mobility of water in the extracellular space is increased. The prolongation
of the T2 component of fluid with extracellular methemoglobin results in hyperintensity on DW images. Hemorrhage
containing deoxyhemoglobin, intracellular methemoglobin, and hemosiderin are hypointense on DW images because of
magnetic susceptibility effects. Because these products of hemorrhage have very low signal intensity on T2-weighted
images, ADCs cannot be reliably calculated for them.
Figure 5. For comparison, A view showing the
hematoma on CT scan, precontrast MRI T1
image, MRI T2, FLAIR and diffusion
Figure 6. For comparison, A view showing
the hematoma on CT scan, precontrast
MRI T1 image, MRI T2, FLAIR and
diffusion weighted images
DIAGNOSIS: HYPERTENSIVE PUTAMENO-CAPSULAR HEMORRHAGE
Haemorrhagic microvascular brain disease constitutes the other facet of the bad coin (the microvascular brain disease)
the first facet of which is the ischemic microvascular brain disease. Both the haemorrhagic and the ischaemic
microvascular brain disease share common haemorheological, metabolic endocrinal abnormalities and cardiac changes
In microvascular brain disease, the small penetrating arterioles of the subependymal and the pial microvascular systems
tend to become stenosed and undergo lipohyalinosis or they may dilate to form microaneurysms. From the pathological
point of view both Lipohyalinosis and microaneurysms, almost invariably, coexist in the same individual, thus making
the patient Liable to develop either the ischaemic or the haemorrhagic microvascular brain diseases.
Figure 7. Microaneurysms of the small penetrating arterioles
Microaneurysmal formation occurs predominantly in the territory of the subependymal microvascular system,thus
making the incidence of the haemorrhagic microvascular events much more frequent in the periventricular gray matter
(thalamus, basal ganglia and the internal capsule) or the immediate periventricular white matter. The coexistence of
lipohyalinosis and microaneurysms in the periventricular regions will explain the propensity of the diseased
microvascular system either to thrombose (resulting in lacunar infarctions) or to rupture and leak resulting in
periventricular haematoma formation. Lacunar infarctions and hypertensive cerebral haemorrhages are two facets of
one and the same bad coin (the microvascular brain disease).
Figure 8. Microaneurysms are predominately
distributed in the immediate periventricular
Microaneurysmal formation should weaken the arteriolar wall so that rupture and leakage can occur even in
normotensive states. When microaneurysmal rupture occurs, the bleeding will result in haematoma formation. The
bleeding will then be arrested by occlusive thrombosis of the bleeding microaneurysms. Following microaneurysmal
rupture and bleeding, the size of the resulting haematoma will be determined by the bleeding time. The bleeding time is
a function of the whole blood viscosity in general and the platelet aggregability in particular.
Should microaneurysmal bleeding occurs during periods of higher blood viscosity, the bleeding time will be shorter and
subsequently the size of the resulting haematoma will be smaller. In fact during high blood viscosity the bleeding is not
infrequently arrested before forming haemorrhages adequate to give rise to immediate clinical sequelae. Patients with
higher blood viscosity and thrombotic tendency, although less likely to develop serious haemorrhagic microvascular
events, they are particularly liable to develop serious ischaemic microvascular events.
During periods of lower blood viscosity and thrombotic tendency of the blood, microaneurysmal bleeding might result in
huge haematoma formation that may split along the planes of the white matter forming a substantial space occupying
clot, or may rupture into the ventricular system resulting in massive ventricular haemorrhage. In general inverse
correlation is present between the haematoma size and the current blood viscosity at the time of microaneurysmal
Patients with microvascular brain disease might have recurrent events which could be purely haemorrhagic or purely
ischaemic, however, it is not uncommon for some patients to fluctuate between the haemorrhagic and the ischaemic
events, developing haemorrhagic events at certain times and ischaemic events at other times. In general ischaemic
microvascular events are much more common and much more frequent than the haemorrhagic events.
PATHOGENESIS OF HYPERTENSIVE CEREBRAL HEMORRHAGE
Hypertension causes fibrinoid necrosis of these penetrating arterioles. The massive intracerebral hemorrhage which is a
complication of hypertension, arises from rupture of a necrotic arteriole or from rupture of a minute quot;miliaryquot;
aneurysm formed at the site of necrosis. These aneurysms were first described by CHARCOT and BOUCHARD. The
frequency of fibrinoid necrosis and miliary aneurysm formation in vessels within basal ganglia and thalamus accounts
for the frequency of intracerebral hemorrhage in those locations. Fibrinoid is identified by its structureless or sometimes
granular red appearance on H&E stain and by the fact that , unlike hyalinized smooth muscle which is also eosinophilic,
the fibrinoid areas stain with stains for fibrin such as PTAH or Putz stain or with certain trichrome stains. The fibrinoid
change in these vessels was called lipohyalinosis by Miller-Fisher in a very influential series of articles. However that
term is confusing because hyalinized arteries are arteries whose media has undergone a pathologic change which is not
fibrinoid necrosis and which by itself does not lead to rupture. Indeed hyalinized arterioles are common in hypertension.
The term lipohyalinosis stresses the presence of fat in the degenerate arteriolar wall but again this change is not the
hallmark of the arterioles that are in danger of rupturing or forming miliary aneurysms. The fibrinoid change is the
critical change in these diseased arteriolar segments looks and stains just like the fibrinoid seen in renal and other
arterioles in malignant hypertension. The important point to remember is that, for unknown reasons, the brain
arterioles can undergo fibrinoid necrosis even in so-called benign hypertension--that is in patents with only modest
blood pressure elevation. For that reason it is important to treat even benign hypertension. The series figures below
illustrates the pathologic processes that can lead to rupture.
Figure 9. A, The figure shows the wall of an arteriole stained with H&E. The amorphous pink [eosinophilic] material in
the wall could be either fibrinoid or amyloid. To prove that it is firbrinpoid the section or its close neighbor should be
stained with any one of several techniques that stain fibrin [e.g. Putz stain-blue; or the PTAH stain-blue; or a trichrome
stain such as the azo carmine stain; the azo carmine is particularly good because it distinguishes fibrinoid from garden
variety hyalinization by staining fibrin/fibrinoid red while staining collagen or hyalinized collagen blue.]. B, This section
was stained with azocarmine. An arteriole in the subarachnoid space has an amorphous red material occupying a good
portion of its wall. This is fibrinoid. Fibrinoid is frequently segmental in distribution so that the entire circumference
may not be involved and other areas along the length of the vessel may also be spared. C, This figure was also stained
with azocarmine. The arteriole wall is replaced by red fibrinoid and displays aneurysmal dilation.
Figure 10. A,B Sometimes a miliary aneurysm thrombosis rather than ruptures. It then appears as a fibrous ball which
may be separated from the parent vessel due to the plane at which the section has been cut. If the section is close to the
parent arteriole there will be elastic tissue at the margin of the ball. This elastic tissue stains black with the VVG stain in
Figure 11. The pathologist got lucky when this section was
taken. Here a miliary aneurysm that has neen converted to a
fibrous ball or globe, shown in this longitudinal section, still
connected to the parent arteriole by a thin neck.
Cerebral Haematomas occur much more frequently at the putameno-capsular and the thalamic regions and may
rupture into the ventricular system. Less common sites include the cortical and the immediate subcortical white matter,
especially in the parietal region, the pons and the cerebellum.
The resulting haematoma is dark red in colour due to the existence of deoxyhaemoglobin inside the intact RBCS. During
the subacute stage (3 days - one month) the dark red colour of the haematoma is replaced by a brownish discoloration,
which starts at the periphery of the haematoma and then extends to its center. This brownish discoloration occurs due to
the replacement of deoxyhaemoglobin by the oxidized methemoglobin.
Acute hematoma usually spreads between white matter tracts resulting in island of viable brain tissues within the
hematoma itself. Bleeding usually stops shortly after the initial ictus, however in a substantial minority of patients the
hematoma continues to expand usually within the first hour after the presentation. Expansion after one hour is unusual.
Once hematoma forms, vasogenic edema forms around the clot as osmotically active serum proteins are released from
the hematoma. Edema peaks at about 48 hours and usually begins to resolve after 5 days. Whether the brain tissues
surrounding the acute hematoma is ischemic -due to vascular compression- or not is controversial. Functional
suppression (diaschisis) of brain activity rather than ischemia is more probable.
Risk of Hematoma Enlargement
In nearly one quarter of initially alert patients presenting with spontaneous intracerebral hemorrhage, secondary
deterioration in level of consciousness occurs within the first 24 hours after onset. Hematoma expansion and edema
formation are believed to be the major factors involved In several large prospective and retrospective studies,
investigators have evaluated the rate of hematoma enlargement after initial presentation and report rates ranging from
14 to 38% within the first 24 hours of admission.[27,28]
In their review of 627 patients with spontaneous intracerebral hemorrhage Fujii, et al.. reported that CT scanning
within 24 hours of admission demonstrated enlargement of the hematoma in 14% of patients. Five factors were found to
be associated with enlargement: admission shortly after onset of symptoms, heavy alcohol consumption, irregularly
shaped hematoma, reduced level of consciousness, and low level of fibrinogen.
Figure 12. Cerebral (A) and pontine (B) acute haemorrhage, C, acute cerebellar hemorrhage
Gradually the haematoma is surrounded by reactive gliosis and macrophages laden with haemosiderin granules (Ferric
hydroxide). The clot is gradually absorbed starting with its periphery and is replaced by a yellow fluid, this is called an
apoplectic cyst. Reactive gliosis progressively increases and ultimately transforms the haematoma into a slit-like scar.
Figure 13. A, acute putameno-capsular & intraventricular hemorrhage, B, apoplectic cyst
Figure 14. A, Subacute caudate hemorrhage, B, apoplectic cyst, C, Hypertensive hemorrhage into basal ganglia region
(specifically: internal capsule).
Pathologically the brains of patients with cerebral haemorrhages very frequently show evidence of past microvascular
ischaemic events such as lacunar infarctions, leukoaraiosis,etc.
INCIDENCE OF COMMON ANATOMICAL SITES IN HYPERTENSIVE INTRACEREBRAL HAEMORRHAGE
Figure 15. Incidence (in % ) of the common anatomical sites in hypertensive intracerebral haemorrhage 28
STRUCTURAL NEUROIMAGING OF MICROVASCULAR CEREBRAL HAEMORRHAGE
CT imaging of haematoma.
A cerebral haematoma, in the acute stage, has higher attenuation values on precontrast scan (hyperdense). The higher
attenuation values of fresh blood is due to the existence of packed haemoglobin in the haematoma. In particular the
globin component of the haemoglobin is responsible for the increased CT density on precontrast scan. With progressive
absorption of haemoglobin, (this usually starts from the periphery of the haematoma) the attenuation value of the
haematoma gradually decreases until the high density haematoma is replaced by a low density space occupying cyst.
Figure 16. A, Acute haematoma, B, an apoplectic cyst and C, an old haematoma (slit-like scar)
The evolution of the haematoma from a high density clot to a low density cyst usually takes a period that ranges between
one month to three months. The walls of this cyst might enhance and the haematoma at this stage might be mixed with
abscess or glioma. History is of paramount significance at this stage. Very old haematoma appears by CT scan as a slit-
like hypodense area with negative mass effect.
In general Haematomas are space-occupying with positive mass effect and are commonly surrounded by a hypodense
oedema area. The most common sites are the putameno-capsular and the thalamic sites and either of them might
rupture intraventricularly. Less common sites includes the parietal lobe, pons and cerebellum.
The diagnosis of acute ICH is virtually 100% reliable with non-contrast CT due to the characteristic mass of blood of
high attenuation value, due to the presence of the globin component of the haemoglobin molecule. Under exceptional
circumstances, patients with profound anaemia, with a haematocrit of 20% or less have presented with an acute
haematoma which was isointense to brain on account of the low haemoglobin contents of the fresh haematoma. Fresh
blood has an attenuation value of 55-85 Hounsfield units, the high attenuation (50-70 Hounsfield units) is from high
protein concentration within intact red blood cells and not iron content 1.
As the fresh clot starts to retract after 24-48 hours from onset, there is serum extrusion around its periphery, resulting
in a ring of hypointensity that surrounds the haematoma . In the subacute stage, the haematoma maintains its mass
effect but becomes progressively less dense, from the periphery toward the center, until reaching isointensity with the
adjacent brain parenchyma. The infusion of intravenous contrast at this stage can demonstrate an area of ring
enhancement at the periphery of the haematoma. In the chronic stage, the mass effect of the haematoma is no longer
present, post-contrast enhancement has disappeared after about 6 weeks from onset , and the residual is a hypointense
cavity, at times in the form of a slit that can be indistinguishable from an area of old cavitated infarction.
More detailed description of the CT scan appearance of brain hemorrhage
The CT appearance of hemorrhage is determined by the degree of attenuation of the x-ray beam, which is proportional
to the density of hemoglobin protein (relative to plasma concentration) within the hematoma.
Immediately following vessel rupture, the hematoma consists of a collection of red blood cells, white blood cells, platelet
clumps, and protein-rich serum that has a heterogeneous appearance on CT with attenuation in the range of 30–60
Hounsfield units (HU), depending on the degree of plasma extrusion . In this hyperacute phase, hemorrhage may be
difficult to distinguish from normal cortex because of similar attenuation. Over minutes to hours, a fibrin clot forms
with an increase in attenuation to 60–80 HU (Fig. 11) . Clot retraction and extrusion of serum can further increase
attenuation to as high as 80–100 HU in the center of the hematoma. The degree of attenuation may be reduced in
patients with severe anemia , impaired clot formation due to coagulopathy, or volume averaging with adjacent
tissue. Vasogenic edema evolves around the hematoma within hours and may continue to increase for up to 2 weeks
after hemorrhage onset .
Figure 17. CT appearance of hemorrhage. Serial CT scans of right
thalamic hematoma. (A) Acute ICH in the right thalamus with mean
attenuation 65 HU. (B) CT performed 8 days later than (A); the periphery
of the hematoma is now isodense to the brain while the center of the
hematoma has mean attenuation 45 HU. (C) CT performed 13 days later
than (A) shows continued evolution of the hematoma with decreasing
attenuation. (D) CT performed 5 months later than (A) shows a small area
of encephalomalacia in the location of the previous hemorrhage.
Over the following days, cells and protein are broken down and scavenged by macrophages, leading to slowly decreasing
attenuation, with the greatest decrease at the periphery of the hematoma and more gradual evolution toward the center
(Fig. 11) . Within 4 to 9 days, the hematoma attenuation decreases to that of normal cortex, and within 2 to 3 weeks
to that of normal white matter .
The CT recognition of subacute intracerebral hematoma can be challenging because the attenuation is similar to that of
normal brain tissue, although mass effect may still be present. MR imaging can confirm subacute hematoma. As time
goes on, attenuation continues to decrease to levels below that of the normal brain. Eventually, the hematoma resolves
into a fluid-filled or slit-like cavity that may be difficult to visualize on CT (Fig. 11). Contrast enhancement is not
present in the initial days following ICH but may develop at the periphery in weeks to months , sometimes leading to
diagnostic confusion with brain tumor or abscess.
A blood-fluid level may be seen in medium to large ICH within the first hours after onset; the dependent portion
displays higher attenuation (Fig. 12) due to sedimentation of cellular elements . This finding may be more common
in ICH caused by anticoagulation , but it is not specific and has also been described in ICH due to hypertension,
trauma, tumor, or arterial-venous malformation. The association with shorter time interval from ICH onset, and in
some cases with anticoagulation, has led to speculation that incomplete clotting is required for blood-fluid level
Figure 18. CT with blood-fluid level. A 77-year-old woman was admitted with coma of 4
hours' duration. CT scan shows massive left hemispheric hematoma with blood-fluid level.
No history of anticoagulation or coagulopathy.
Box 1. As the hemorrhage evolves, different characteristic appearances can be identified on CT, depending on the age of
the bleed. CT findings over time are as follows:
After 7-10 days, the high density of blood begins to decrease, starting from the periphery of the lesion.
From 1-6 weeks, peripheral enhancement can be seen, mimicking the appearance of an abscess, possibly related
to hypervascularity at the periphery of a resolving hematoma or disruption of the blood-brain barrier.
By 2-4 months, decreased density indicates cavity formation. A residual cavity is the final stage, which is reached
after complete absorption of necrotic and hemorrhagic tissue.
MRI Imaging of cerebral haematoma
Imaging of haematoma by MRI is time dependent as follow:
The hyperacute stage (0 - 12 hour)
The acute hematoma less than 12 hours old is composed mostly of intracellular oxyhemoglobin with the edematous brain
undergoing necrosis. 1 On T2-weighted MR images, hyperacute hematoma will exhibit inhomogeneous signal due to
hypointense deoxyhemoglobin and hyperintense, edematous cortical tissue. MR is less sensitive than CT in the
hyperacute stage because diamagnetic intra- cellular oxyhemoglobin lacks unpaired electrons and thus clot signal is
close to normal brain parenchyma- normal to slightly lower signal on TI-weighted images and slightly higher signal on
T2-weighted images 2,3. Repeat imaging is indicated to monitor the size of the hemorrhage and the development of
delayed hemorrhage and vasogenic edema.
The acute stage (12 Hr - 3 days)
Due to the presence of the magnetically susceptible deoxyhaemoglobin. The T2 relaxation time will be markedly
shortened, so that fresh blood appears hypointense (black) on the T2 weighted MRI images. This hypointensity is
commonly surrounded by a wider hyperintense area that represents oedema. On the T1 weighted images fresh blood
appears isointense or slightly hyperintense.
Acute hematoma one to three days old are composed mostly of paramagnetic intracellular deoxyhemoglobin. The
deoxyhemoglobin is formed by the dissociation of oxygen from hemoglobin, a process that begins within several hours.
Because the deoxyhemoglobin within intact, clotted hypoxic red blood cells does not cause T1 shortening, the hematoma
will have normal to slightly lower signal on TI-weighted MR images. The concentration of red blood cells with clot and
the concentration of fibrin cause T2 shortening, with areas of very low signal on T2-weighted spin echo and T2 * -
weighted gradient echo images 3.
Figure 19. A 62-year-old female with hypertension presented with
acute-onset ataxia and confusion. Noncontrast CT exam of the head
[left image] showed a large, right cerebellar hemorrhage, which was
evacuated to relieve the mass effect on the brainstem and fourth
ventricle. The cerebellar hemorrhage is seen hypointense on the T2
image due to Deoxyhemoglobin [right image].
Figure 20. The concentration of red blood cells with clot and the concentration of
fibrin cause T2 shortening, with areas of very low signal on T2-weighted spin echo
and T2 * -weighted gradient echo images
The subacute stage (3 days - one month)
The picture of hematoma is determined by the oxidation of deoxyhemoglobin to methemoglobin and its shift from the
intracellular to the extracellular compartment. The picture of haematoma, during this period is governed by the
progressive reduction in the concentration of deoxyhaemoglobin and the progressive increase in the concentration of the
oxidized methemoglobin. These changes take place from the periphery of the haematoma to its center. Intracellular
oxidized methemoglobin induces shorting of T2 relaxation time while extracellular oxidized methemoglobin induces
prolongation of T2 relaxation time
Progressive reduction in the concentration of deoxyhaemoglobin and shift of oxidized methemoglobin from the
intracellular to the extracellular compartment, due to lyse of RBCs, results in progressive disappearance of the T2
hypointensity observed in the acute stage. Absence of the deoxyhaemoglobin and appearance extracellular oxidized
methemoglobin will result in progressive prolongation of the T2 relaxation time that starts from the periphery of the
haematoma to its center, this results in progressive increase of the T2 signal intensity (it becomes brighter); At first the
periphery of the haematoma becomes brighter on the T2 weighted images, and this brightness progressively extends to
Within a few days, the subacute hematoma start to undergo liquefaction with development of vasogenic edema. As the
edema increases over the first week, it may be great enough to cause herniation. The edema has fluid or water
characteristics: iso- to hypointense on TI-weighted images, and hyperintense on T2-weighted images. With oxidation of
deoxyhemoglobin to strongly paramagnetic intracellular methemoglobin, proton-electron dipole-dipole interactions
between hydrogen atoms and the paramagnetic centers of methemoglobin will cause marked TI shortening and very
high signal intensity on TI-weighted images 4 within the periphery of the hematoma. The intracellular methemoglobin
will cause T2 shortening and very low signal on T2-weighted images.
After erythrocyte membrane breakdown and extracellular migration of methemoglobin, there is neovascularization with
removal of blood components and debris by macrophages. The new blood vessels at the periphery of the lesion lack the
tight endothelial junctions of an intact blood brain barrier, and so there is intense enhancement of the margins on both
contrast CT and MR 1. The fragile granulation tissue vessels predispose the patient to additional episodes of acute
hemorrhage. CT will show a decrease in the density of the hemorrhage and decrease in the mass effect, the latter due to
a decrease in edema. MR will exhibit the persistent high signal of extracellular methemoglobin on TI - and T2-weighted
images 4 for up to a year. The peripheral rim of hemosiderin and ferritin has slightly low signal on Tl- and marked low
signal on T2-weighted images [201 from the susceptibility effect of hemosiderin within macrophage lysosomes.
Figure 21. MRI T2 image (A) and proton density image (B) showing a subacute haematoma, notice the peripheral
hypointense hemosiderin ring
Because the extracellular oxidized methemoglobin has a paramagnetic quality it results in shortening of the T1
relaxation time, so that the haematoma in the subacute stage appears hyperintense (bright) on the T1 weighted MRI
images. This again starts from the periphery of the haematoma and progresses to its center, because as mentioned
before methemoglobin starts to appear at the periphery of the haematoma, this results initially in ring hyperintensity on
the T1 images.
Figure 22. Early subacute hemorrhagic contusion in a 78-year- old male. Sagittal TI-weighted image demonstrates high
signal intensity at the periphery of the hematoma, consistent with intracellular methemoglobin.
The haemosiderin pigmentation that surrounds the haematoma in the subacute and
chronic stages is responsible for the rim of hypointensity that surrounds the haematoma
on the T2 weighted and proton density images.
Figure 23. The hypointense hemosiderin ring of subacute haematoma
Chronic stage (one month to 3 months)
Due to complete absorption of the deoxyhaemoglobin and diffuse and homogeneous increase of the oxidized
methemoglobin within the haematoma; it appears diffusely hyperintense (bright) on both the T1 and T2 weighted
Clot resorption begins from the periphery inward, and depending on the size of the hematoma, may vary from one to six
weeks in duration. Necrotic tissue is sloughed and cystic cavities are formed over the next 6 to 12 months. Focal atrophy
is characterized by a decrease in the size of cortical gyri, with compensatory enlargement of cerebrospinal fluid spaces
and dilatation of the adjacent ventricle. Cystic cavities are surrounded by gliosis and hemosiderin scarring.
The hematoma biochemical stages
Table 1. The MRI biochemical stages of cerebral hematomas
Biochemical substance MRI changes
Oxyhemoglobin Oxyhemoglobin lacks unpaired electrons and thus clot signal is close to normal
brain parenchyma- normal to slightly lower signal on TI-weighted images and
slightly higher signal on T2-weighted images
Paramagnetic intracellular Because the deoxyhemoglobin within intact, clotted hypoxic red blood cells does
deoxyhemoglobin. not cause T1 shortening, the hematoma will have normal to slightly lower signal
on TI-weighted MR images. The concentration of red blood cells with clot and
the concentration of fibrin cause T2 shortening, with areas of very low signal on
T2-weighted spin echo and T2 * -weighted gradient echo images
Paramagnetic intracellular Proton-electron dipole-dipole interactions between hydrogen atoms and the
methemoglobin. paramagnetic centers of methemoglobin will cause marked TI shortening and
very high signal intensity on TI-weighted images within the periphery of the
hematoma. The intracellular methemoglobin will cause T2 shortening and very
low signal on T2-weighted images.
Extracellular migration of MR will exhibit the persistent high signal of extracellular methemoglobin on TI
methemoglobin. - and T2-weighted images for up to a year. The peripheral rim of hemosiderin
and ferritin has slightly low signal on Tl- and marked low signal on T2-
weighted images  from the susceptibility effect of hemosiderin within
Clot resorption begins from the Focal atrophy is characterized by a decrease in the size of cortical gyri, with
periphery inward, and depending on compensatory enlargement of cerebrospinal fluid spaces and dilatation of the
the size of the hematoma, may vary adjacent ventricle. Cystic cavities are surrounded by gliosis and hemosiderin
from one to six weeks in duration. scarring.
Necrotic tissue is sloughed and cystic
cavities are formed over the next 6 to
Table 2. The biochemical stages of cerebral hematomas
Hyperacute stage [0-12 Immediately after an intracerebral bleed, the liquefied mass in the brain substance
Hr] contains oxyhemoglobin but no paramagnetic substances. Therefore, it looks like any other
proteinaceous fluid collection.
Reduction in oxygen tension in the hematoma results in the formation of intracellular
deoxyhemolobin and methemoglobin in intact red cells. These substances have a
Acute stage [4Hr -3 days]
paramagnetic effect that produces T2 shortening. A thin rim of increased signal
surrounding the hematoma on T2-weighted images represents edema.
As red blood cells lyse, redistribution of methemoglobin into the extracellular space
changes the effect of this paramagnetic substance to one of predominantly T1 shortening.
Subacute stage [3days-3 The longer T2 results from(1) a combination of red blood cell lysis (T2 shortening
weeks] disappears), (2) osmotic effects that draw fluid into the hematoma, and (3) the repetition
times (TR) that are in general use for T2-weighted sequences, which are not sufficiently
long to eliminate T1 contrast effects in the image.
Phagocytic cells invade the hematoma (starting at the outer rim and working inward),
Chronic stage[3 weeks-3
metabolizing the hemoglobin breakdown products and storing the iron as
superparamagnetic hemosiderin and ferritin.
Table 3. Effect of blood products on the MRI signal
lacks unpaired electrons and thus clot signal is close to
Hyperacute stage [0-12 Hr] Oxyhemoglobin normal brain parenchyma- normal to slightly lower signal
on TI-weighted images and slightly higher signal on T2-
T2 shortening, with areas of
Deoxyhemoglobin within very low signal on T2-
Acute stage [4Hr -3 days] intact, clotted hypoxic red No effect weighted spin echo and T2 *
blood -weighted gradient echo
TI shortening and very high
Strongly paramagnetic methemoglobin will cause T2
Early subacute stage [3days- signal intensity on TI-
intracellular shortening and very low
3 weeks] weighted images within the
methemoglobin, signal on T2-weighted
periphery of the hematoma
MR will exhibit the persistent high signal of extracellular
Late subacute stage [3days-3 extracellular migration of
methemoglobin on TI - and T2-weighted images for up to a
Focal atrophy is characterized by a decrease in the size of cortical gyri, with
Chronic stage[3 weeks-3
compensatory enlargement of cerebrospinal fluid spaces and dilatation of the adjacent
ventricle. Cystic cavities are surrounded by gliosis and hemosiderin scarring.
Table 4. Effect of blood products on the MRI signal
Phase Time Hemoglobin T1 T2
Hyperacute <24 hours Oxyhemoglobin Iso or hypo Hyper
Acute 1-3 days Deoxyhemoglobin Iso or hypo Hypo
Early subacute >3 days Methemoglobin Hyper Hypo
Late subacute >7 days Methemoglobin Hyper Hyper
Chronic >14 days Hemosiderin (extracellular) Iso or hypo Hypo
Hyperacute Hyperacute hemorrhage refers to a collection of blood in which oxyhemoglobin predominates.
Hemorrhage (0 TO This type of hemorrhage is rarely encountered in the clinical setting because several hours
12 Hours) commonly elapse between the onset of hemorrhage and a patient being referred for MR imaging.
A hyperacute hematoma may have a nonspecific appearance on MR imaging because
oxyhemoglobin is not paramagnetic. Hyperacute hemorrhages can behave similar to other lesions
with increased water content and are typically isointense or low signal on Tl-weighted images and
high signal on T2- weighted images.With clot retraction in the hyperacute phase, the increased
protein content of the hemorrhage results in the lesion being isointense to hyperintense on Tl-
weighted images, which can facilitate differentiation from other mass lesions. A hypointense rim
along the periphery of a hyperacute hemorrhage was noted, and this may provide an additional
clue to the diagnosis. Hyperacute hemorrhage, however, is more readily identified on CT, which
remains the initial examination of choice for its evaluation.
Acute Hemorrhage In the acute setting, there is clot retraction and resorption of serum. As the hematoma becomes
(12 Hours to 3 isolated from the normal cerebral circulation, oxyhemoglobin rapidly deoxygenates to yield
Days) deoxyhemoglobin. The increased protein content of the retracted clot, which is responsible for the
high attenuation noted on noncontrast CT, causes the hematoma to be slightly hyperintense
relative to low-intensity cerebrospinal fluid (CSF) and slightly hypointense to brain parenchyma
on Tl-weighted images. In contrast to CT in the acute setting, which reliably demonstrates high
attenuation characteristic of acute hemorrhage, MR imaging findings on Tl-weighted images are
T2-weighted images demonstrate a marked decrease in signal intensity because of magnetic
susceptibility effects. The signal loss is due to local field inhomogeneity related to paramagnetic
deoxyhemoglobin within intact red blood cells. Gradient echo images exaggerate this effect and
are often useful for the diagnosis of acute hemorrhage
Subacute In the early subacute stage, oxidation of deoxyhemoglobin to methemoglobin occurs within intact
Hemorrhage: red blood cells. Methemoglobin is paramagnetic, which results in marked increased signal
Early (3 Days to I intensity on Tl-weighted images. Typically the increased signal begins at the periphery of the clot
Week) and progresses inward. The differential diagnosis of lesions that demonstrate increased signal
intensity on noncontrast TI-weighted images is relatively limited. Fat; substances with elevated
protein content (mucus or fluid within certain intracranial tumors, i.e., craniopharyngioma); and
paramagnetic moieties, such as melanin, free radicals (within the wall of parenchymal abscesses),
and ions including calcium, manganese, and copper, can exhibit high signal intensity on Tl-
weighted images. Correlation with the clinical history, morphology, and location of the lesion as
well as appearance on other imaging sequences (i.e., T2, gradient echo, and fat suppression)
typically allows differentiation from subacute hemorrhage.
On T2-weighted images, paramagnetic methemoglobin in intact red blood cells results in low
signal intensity similar to that of deoxyhemoglobin. The combination of bright signal intensity on
Tl and markedly decreased signal intensity on T2 is relatively specific for paramagnetic substances
and, with the appropriate morphology, is highly suggestive of intracranial hemorrhage
Subacute The late subacute stage is characterized by lysis of the blood cells. Concurrently, there is dilution
Hemorrhage: Late of extracellular methemoglobin and breakdown of the proteinaceous clot. High signal intensity
(1 Week to persists on TI-weighted images because of methemoglobin; however, lysis of the red blood cells
Months) and the decrease in protein content result in increased signal intensity on T2-weighted images.
Bright signal intensity on both Tl-weighted and T2- weighted images is highly specific for
hemorrhage. Furthermore, at the periphery of the hemorrhage, early accumulation of
hemosiderin and ferritin within macrophages causes a low signal intensity ring, most prominent
on T2-weighted images.
Chronic stage The hallmark of chronic hemorrhage is low signal intensity on T2-weighted images because of
(Months to Years) ferritin and hemosiderin within macrophages, which are the final breakdown products of
hemoglobin. The resulting low intensity first appears during the late subacute stage of hematoma
evolution at the margin of the lesion. With time, the rim thickens. A collapsed cavity with
peripheral areas of low signal intensity on T2-weighted images is the residuum of an
uncomplicated intraparenchymal hemorrhage. This appearance can persist indefinitely.
A new version of this PDF file (with a new case) is uploaded in my web site every week (every Saturday and
remains available till Friday.)
To download the current version follow the link quot;http://pdf.yassermetwally.com/case.pdfquot;.
You can also download the current version from my web site at quot;http://yassermetwally.comquot;.
To download the software version of the publication (crow.exe) follow the link:
The case is also presented as a short case in PDF format, to download the short case follow the link:
At the end of each year, all the publications are compiled on a single CD-ROM, please contact the author to know
Screen resolution is better set at 1024*768 pixel screen area for optimum display.
For an archive of the previously reported cases go to www.yassermetwally.net, then under pages in the right panel,
scroll down and click on the text entry quot;downloadable case records in PDF formatquot;
1. New PF, Aronow S. Attenuation measurements of whole blood and blood fractions in computed tomography.
2. Atlas SW, Thulbom KR. MR detection of hyperacute parenchymal hemorrhage of the brain. Am J Neuroradiol
3. Gomori JM, Grossman RI, Goldberg HI, et al. Intracranial hematomas: imaging by high-field MR. Radiology
4. Wilberger JE, Rothfus WE, Tabas J, et al. Acute tissue tear hemorrhages of the brain: computed tomography and
clinicopathological correlations. Neurosurgery 1990;27:208-13.
5. Barnett HJM, Yatsu FM, Mohr JP, Stein BM, eds.: Stroke: Pathophysiology, Diagnosis, and Management. 3rd ed.
Churchill Livingstone; 1998.
6. Bradley WG Jr: MR appearance of hemorrhage in the brain. Radiology 1993 Oct; 189(1): 15-26.
7. Broderick JP, Brott T, Tomsick T: Intracerebral hemorrhage more than twice as common as subarachnoid
hemorrhage. J Neurosurg 1993 Feb; 78(2): 188-91.
8. roderick JP, Brott TG, Duldner JE: Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-
day mortality. Stroke 1993 Jul; 24(7): 987-93.
9. Challa VR, Moody DM, Bell MA: The Charcot-Bouchard aneurysm controversy: impact of a new histologic
technique. J Neuropathol Exp Neurol 1992 May; 51(3): 264-71.
10. Chan S, Kartha K, Yoon SS: Multifocal hypointense cerebral lesions on gradient-echo MR are associated with
chronic hypertension. AJNR Am J Neuroradiol 1996 Nov-Dec; 17(10): 1821-7.
11. Fazekas F, Kleinert R, Roob G: Histopathologic analysis of foci of signal loss on gradient-echo T2*- weighted MR
images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds.
AJNR Am J Neuroradiol 1999 Apr; 20(4): 637-42.
12. Gokaslan ZL, Narayan RK: Intracranial Hemorrhage in the Hypertensive Patient. Neuroimaging Clinics of North
America 1992; 2: 171-86.
13. Gomori JM, Grossman RI: Mechanisms responsible for the MR appearance and evolution of intracranial
hemorrhage. Radiographics 1988 May; 8(3): 427-40.
14. Nelson JS, Parisi JE, Schochet SS Jr: Principles and Practise of Neuropathology. Mosby - Year Book, Inc. St. Louis,
15. Robertson CS, Contant CF, Gokaslan ZL: Cerebral blood flow, arteriovenous oxygen difference, and outcome in
head injured patients. J Neurol Neurosurg Psychiatry 1992 Jul; 55(7): 594-603.
16. Ruscalleda J, Peiro A: Prognostic factors in intraparenchymatous hematoma with ventricular hemorrhage.
Neuroradiology 1986; 28(1): 34-7.
17. Spangler KM, Challa VR, Moody DM: Arteriolar tortuosity of the white matter in aging and hypertension. A
microradiographic study. J Neuropathol Exp Neurol 1994 Jan; 53(1): 22-6.
18. Taveras JM, Pile-Spellman J: Neuroradiology. 3rd ed. Williams & Wilkins; 1996.
19. Welch KMA, Caplan LR, Reis DJ, Weir B, Siesjo BK, eds.: Primer on Cerebrovascular Diseases. Morgan
20. Bergstrom M, Ericson K, Levander B, et al.. Variation with time of the attenuation values of intracranial
hematomas. J Comput Assist Tomogr. 1977;1(1):57–63.
21. Kasdon DL, Scott RM, Adelman LS, et al.. Cerebellar hemorrhage with decreased absorption values on computed
tomography: a case report. Neuroradiology. 1977;13(5):265–266.
22. Inaji M, Tomita H, Tone O, et al.. Chronological changes of perihematomal edema of human intracerebral
hematoma. Acta Neurochir Suppl. 2003;86:445–448.
23.Messina AV. Computed tomography: contrast enhancement in resolving intracerebral hemorrhage. AJR Am J
24. Ichikawa K, Yanagihara C. Sedimentation level in acute intracerebral hematoma in a patient receiving
anticoagulation therapy: an autopsy study. Neuroradiology. 1998;40(6):380–382.
25. Pfleger MJ, Hardee EP, Contant CF, et al.. Sensitivity and specificity of fluid-blood levels for coagulopathy in acute
intracerebral hematomas. AJNR Am J Neuroradiol. 1994;15(2):217–223.
26. Dolinskas CA, Bilaniuk LT, Zimmerman RA, et al.. Computed tomography of intracerebral hematomas. I.
Transmission CT observations on hematoma resolution. AJR Am J Roentgenol. 1977;129(4):681–688.
27. Fujii Y, Takeuchi S, Sasaki O, et al: Multivariate analysis of predictors of hematoma enlargement in spontaneous
intracerebral hemorrhage. Stroke 29:1160–1166, 1998
27. Kazui S, Naritomi H, Yamamoto H, et al: Enlargement of spontaneous intracerebral hemorrhage. Incidence and
time course. Stroke 27:1783–1787, 1996
28. Metwally, MYM: Textbook of neurimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for
electronic publishing, version 9.1a January 2008